Childhood-onset Obsessive-compulsive disorder (OCD) and tic disorders, including Tourette disorder, arise from a variety of etiologies. A subgroup of patients with symptom exacerbations triggered by Group A beta-hemolytic streptococcal infections (GABHS) has been identified and labelled PANDAS for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections. Systematic studies of phenomenology, treatment and prevention are ongoing. Over 50 children and adolescents have been examined and their clinical presentation reported (1). The children are young (average age of symptom onset = 6.5 years), predominantly male (boys: girls = 2.6:1) and by definition, have an episodic course with symptom exacerbations associated with GABHS infections. Two studies were completed during the reporting period. The first examined the effectiveness of immunomodulatory treatments - plasmapheresis and intravenous immunoglobulin (IVIG) in comparison with placebo (sham IVIG) treatment. Data analysis is near completion for the first 29 subjects and preliminary results show that the active treatments were strikingly and significantly superior to placebo, with the average improvement exceeding 50% on some measures at one-month follow-up. The second study, an eight month long double-blind crossover trial, examined the effectiveness of penicillin prophylaxis for prevention of symptom exacerbations in children with PANDAS. Penicillin was slightly better than placebo in preventing GABHS infections and in improving overall behavior. Of interest, antistreptococcal titers rose frequently in both phases of the study. Although poor compliance might be blamed, the break-through infections suggest that PenV-K may not be sufficient prophylaxis against GABHS for rheumatic fever, as well as PANDAS.